Stroke is the third most common cause of death in the United States. Despite progress in understanding molecular mechanisms of cell death after stroke, widely effective stroke treatment remains elusive. Recent studies on neurogenesis, the development of neurons from immature precursor cells, suggest that it might be possible for dead or injured neural cells to be replaced through this process. Support for this possibility includes evidence that neurogenesis continues to occur in the brains of adult mammals, including mice (Lim et al. (2000) Neuron, 28(3): 713-726; Yoshimura et al. (2001) Proc Natl Acad Sci USA, 98(10): 5874-5879), rats (Jin et al. (2001) Proc Natl Acad Sci USA, 98(8): 4710-4715; Liu et al. (1998) J Neurosci, 18(19): 7768-7778), non-human primates (McDermott et al. (1991) J Anat, 1991. 178: 45-63) and humans (Eriksson et al. (1998) Nat Med, 1998. 4(11): 1313-1317). Neural precursor cells include both self-renewing, totipotent “stem” cells and pluripotent “progenitor” cells, which can be isolated from adult brains and expanded in vitro (Fricker et al. (1999) J Neurosci, 1999. 19(14): 5990-6005; Gage et al. (1995) Proc Natl Acad Sci USA, 92(25): 11879-11883; Uchida et al. (2000) Proc Natl Acad Sci USA, 97(26): 14720-14725). These cells can subsequently be transplanted into the brain, where they are able to migrate extensively and to differentiate into neurons and glia (Suhonen et al. (1996) Nature, 1996. 383(6601): 624-627). This raises the intriguing possibility that neural precursor cells might be beneficial in the treatment of CNS diseases, including stroke.
Neural precursor cells transplanted into local regions of the brain can differentiate into neurons, and have the potential to improve symptoms in disorders like Parkinson's disease (Herman, et al. (1992) Curr Opin Neurobiol, 2(5): 683-689; Bjorklund (1992) Curr Opin Neurobiol, 2(5): 683-689; Gage (2000) Science, 287(5457): 1433-1438). However, there are several disadvantages of intracerebral neural precursor cell transplants. First, surgical transplantation may result in local tissue damage or stroke. Second, large numbers of neural precursors from fetal tissues are difficult to obtain. Third, the use of precursors from certain sources, such as human embryos, is ethically and politically controversial. Fourth, neural degeneration in some CNS diseases is extensive, multifocal or even global, which may require widespread replacement beyond the capabilities of surgical transplantation. Finally, intracerebral transplantation may be associated with adverse effects related to the unregulated function of ectopic tissue (Freed et al. (2001) N Engl J Med, 344(10): 710-719).